Prostaglandin derivatives are one of the known poorly soluble drugs and are administered via ophthalmic route for treating elevated intraocular pressure. One of the prostaglandin derivatives, latanoprost has been approved in the United States of America for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, and is commercially available in the United States of America, under the brand name of XALATAN®. XALATAN® Sterile Ophthalmic Solution is a clear, isotonic, sterile, buffered aqueous solution of latanoprost 0.005% (50 μg/ml) with 0.02% benzalkonium chloride and other excipients, and having a pH of approximately 6.7 and an osmolarity of approximately 267 mOsmol/Kg. It is supplied in clear low density polyethylene bottle with a clear low-density polyethylene dropper tip, a turqouise high density polyethylene screw cap and a tamper-evident clear low-density polyethylene overcap. It is recommended for this product that the unopened bottles be stored under refrigeration at a temperature of approximately 2-8° C. and during shipment to the patient, the bottle may be maintained at temperature up to 40° C. for a period not exceeding 8 days. Once the bottle is opened for use, it may be stored at room temperature up to 25° C. for 6 weeks.
Another prostaglandin derivative, which has been approved in the United States of America for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension is unoprostone isopropyl. It is commercially available under the brand name of RESCULA®. RESCULA® is a sterile, isotonic, buffered aqueous solution of unoprostone isopropyl 0.15%, with 0.015% benzalkonium chloride and other excipients and having a pH of approximately 5.0-6.5 and an osmolality of 235-300 mOsmol/kg. It is supplied in clear, natural polypropylene bottle with a natural polypropylene dropper tip, a turquoise polypropylene closure and a clear tamper-evident shrink band. The recommended storage temperature for the product is between 2° C. to 25° C.
A pharmaceutical composition suitable for ophthalmic use is generally filled in small volume containers made up of plastics such as polypropylene and polyethylene rather than rigid materials like glass. Glass is not suitable for making containers for ophthalmic use because it is generally not able to meet requirement of dispensing ophthalmic preparations in very small volumes, for example drops.
The prostaglandin derivatives are known to be unstable either because of absorption or adsorption or degradation, when stored in polyethylene containers. For example, United States patent U.S. Pat. No. 6,235,781 (herein after referred to as '781) shows that when the aqueous composition of prostaglandin is stored in polyethylene containers, percentage drug remaining was about 80% indicating loss of the prostaglandin derivatives. The '781 patent discloses a method of increasing the stability of an aqueous prostaglandin composition comprising a prostaglandin and a pharmaceutically acceptable surfactant wherein the method comprises: packaging the aqueous prostaglandin composition in a polypropylene container, provided that the polypropylene container is not packaged in a bag containing an iron oxide oxygen scavenger.
Another prior art, U.S. patent application No. 20050287325 (hereinafter referred to as '325) discloses that latanoprost is prone to sorption onto the naturally derived plastic containers. The '325 patent application claims a container comprising prostaglandin compositions that exhibit less than 20% sorption of the prostaglandin. The containers are restricted to those made of specific polyolefins, such as DuPont® 20 LDPE, Chevron 5502 HDPE, Atofina 3020 PP, polypropylene homopolymers, low ethylene content (<8%) polypropylenes, and polymers (HDPE, PP) with low content of additives (<5%) and with low flexural modulus (<200 kpsi).
U.S. patent application US20060100288 (herein after referred to as '288) discloses an oil in water type emulsion, which comprises colloid particles having an oily core surrounded by an interfacial film, wherein said interfacial film has an overall positive charge and comprises:                1) 0.001% to 0.1% by weight of a cationic agent,        2) 0 to 1% by weight of a non ionic surfactant, and        3) 0 to 0.5% by weight of an anionic surfactant,with at least one of said ionic surfactant and of said anionic surfactant being present. The patent application discloses the use of polyethylene glycol hydroxystearate as one of the non-ionic surfactant that should be used in combination with a cationic agent.        
In an attempt to develop a pharmaceutical composition of prostaglandin or its derivatives which can be effectively stored in natural polyethylene containers without any drug loss, the inventors surprisingly found that when the prostaglandin derivatives were formulated with polyethylene glycol hydroxystearate, the sorption problem was reduced substantially. When small amount of oil was added to this pharmaceutical composition, the sorption of prostaglandin derivatives to the polyethylene containers was further reduced. It was also found that an addition of a very small amount of oil gave a pharmaceutical composition comprising prostaglandin and polyethylene glycol hydroxystearate that is non irritant to the ocular mucosa, with improvement in the sorption problem, i.e, no sorption of prostaglandin derivatives onto the low density polyethylene containers.